Neurology PSTP Scholars

Research Interests:

My interest in further understanding mechanisms of disease etiology with long-term hopes of improving outcomes makes the PSTP a vital outlet for channeling my long-term aspirations of being a clinician-scientist. I was first interested in research by doing a program at Boston University with Dr. Andrew Budson at the Boston VA, where we looked at reducing false alarms using metacognitive cues in the Mild Cognitive Impairment/Alzheimers Disease population. During my third year, while witnessing an adverse patient outcome, I found myself intrigued by mechanisms of disease in preeclampsia. I received a Howard Hughes Medical Institute Medical Student Fellowship for 2012-2013, where I further fleshed out my research interest under the guidance of Dr. Ananth Karumanchi and Dr. Augustine Rajakumar in limiting pathologic phenomena of this condition of pregnancy. This experience convinced me to enter science, as I felt no better intellectual exhilaration than discovering mechanisms of disease and to translating these observations to potential patient therapies. Lastly, I also did work under the guidance of Dr. Georgia Montouris in medical school looking at major congenital malformations in children of pregnant women on antiepileptic drugs. I hope to further contribute to our understanding of neurologic disease over my time in the PSTP and beyond.

Research Interests:

I earned my medical degree at Rush University Medical College in 2009. I then completed residency in Neurology through Harvard Medical School (Massachusetts General Hospital and Brigham & Women’s Hospital). I now see patients with movement disorders as part of a 2-year clinical fellowship at Northwestern. My primary research interest is the study of Complementary and Alternative Medicine (exercise, meditation, acupuncture, Chinese medicine, and other modalities) for Parkinson’s disease and other movement disorders. With quality-of-life as a major end-point, I expect to find new and innovative ways of improving the health and daily lives of my patients.  I hope to expand the field of neurology beyond the boundaries of Western science, and I am confident that significant progress with regards to disability can be achieved through integration of philosophical principals found in many alternative medicine modalities. Through my pursuit of a Master's of Science in Clinical Investigations I plan to approach these modalities with scientific rigor and improve the quality of life of patients with movement disorders in measurable ways.

Research Interests:

I did medical school at the University of Delhi (Maulana Azad Medical College), India. During medical school I did research work in tuberculosis (TB), studying health seeking delay by patients as well as delay in correctly diagnosing TB by physicians. Interestingly we found this delay varies based on the site of TB i.e. pulmonary Vs extrapulmonary as well as the fact whether it is a private clinic or a city hospital. This small study helped me realize that an in-depth knowledge of evidence based medicine will be essential if I hope to contribute in finding better treatments. I came to US to do an MPH at Harvard School of Public Health where I concentrated in quantitative methods. This involved an in-depth study of epidemiology, biostatistics and clinical trials.

This was also the time when I learnt about the MD-PhD programs and wished I was part of one but they are non-existent in my country. I felt that the rigorous curriculum and the depth of focus of a PhD would provide me with a strong foundation in neuroscience research. My doctoral research with Professor Craig Montell focused on using the fruit fly, Drosophila melanogaster, as a genetic model to elucidate mechanisms of phototransduction. We identified a novel pathway through which Rhodopsin couples with a small G-protein Rac2 to mediate arrestin translocation. This pathway assists in photoreceptor adaptation when an organism moves from a dimly-lit to brightly-lit environment. I later studied the visual pigment metabolic pathway by creating gene knockouts in two novel retinal dehydrogenases mutations of which have been found in hereditary forms of retinal degeneration. In addition, I conducted a very productive genetic screen using RNA interference (RNAi) to identify novel genes involved in retinal- and neuro-degeneration.

I remain interested in continuing basic science research in a neurological disease area during my residency and one of the reasons why I decided to come to Northwestern was the Physician-Scientist Training Program that nurtures physicians to help them transition into independent investigators as well as academic physicians. This dual track of a physician and scientist is longer than a conventional MD track and has its unique challenges. I am confident that the structured and supported environment that the program offers will be crucial for my success.

Research Interests:

The basic question that has driven my career as a clinician scientist is the understanding of the molecular mechanisms underlying hereditary demyelinating and acquired peripheral neuropathies. I had several years of experience in basic science research, at Wayne State University and at Harvard Medical School, studying the biology of myelin and the pathogenesis of demyelinating disease in the Central and Peripheral Nervous System.

In order to be able to pursue translational research, I started the Neurology Residency Program at Northwestern University. During this time, I acquired the clinical skills and the knowledge required to become a Neurologist. I had particular interest in Neuromuscular Diseases and Peripheral Neuropathies including Painful Peripheral Neuropathies. In the Foundation for Peripheral Neuropathy Comprehensive Care Clinic at Northwestern University, I had the possibility to see many patients affected by painful diabetic neuropathy and I realized how little I could help with the current therapies. Given my background in molecular biology of peripheral nerve it was evident that only a better understanding of the molecular mechanisms underlying neuropathic pain in diabetes can lead to a potential treatment for this prevalent affliction.

In the rich academic environment of Northwestern University, I cultivated my interest in chemokine and neuropathic pain in diabetes. I learned about the role of chemokines in the pathogenesis of pain, when listening to a seminar of Dr. Richard Miller, a pioneer in the field. The extremely supportive Neurology Department Chairman, Dr. Kessler and Neurology Residency Program Director, Dr. Simuni, allowed me to start to investigate these questions during my residency program. In fact the National Institute of Neurological Disorders and Stroke recognized the importance of physician scientist education and Northwestern Memorial Hospital ’s leadership in this area by awarding the Department of Neurology the highly competitive NINDS Neuroscience Research Education Program at Northwestern (R25 grant) for 5 years. The R25 grant is designed to foster the development of clinician neuroscientists in the Departments of Neurology at Northwestern University’s Feinberg School of Medicine (NUFSM) to ensure that highly trained scientists will make future advances that lead to a reduction in the burden of neurological disease.

I was the first R25 grant awardees and in the PGY-3 of my Neurology Residency program I started to work in Prof. Richard Miller’s  laboratory. My interest in painful diabetic neuropathy, inspired me to explore the role of chemokines in the pathogenesis of neuropathic pain in diabetes.

Diabetes affects 25.8 million people in the USA and neuropathic pain is present in 3 of 10 individuals with diabetes with a substantial impact on the quality of life. Despite this significant impact and prevalence, current therapies for neuropathic pain are only partially effective in diabetic patients. Moreover, the pathogenesis and the molecular mechanisms underlying neuropathic pain associated with diabetes are not well understood.

We hypothesized that chemokine and in particular stromal-derived-factor-1 (SDF-1) and its receptor (CXCR4) signaling has a role in the pathogenesis of neuropathic pain in diabetes. In our preliminary results, we demonstrated that intra-peritoneal administration of the specific CXCR4 antagonist, AMD3100, reverses neuropathic pain in a mouse model of diabetes type-II, the High-Fat-Diet (HFD)-induced diabetic mouse demonstrating that SDF-1/CXCR4 signaling is necessary for induction and maintenance of neuropathic pain in this animal model of diabetes. Following these observations we were interested to investigate the consequences of CXCR4/SDF-1 signaling on HFD-induced diabetic DRG sensory neurons excitability.

Dr Miller’s laboratory and others have already shown that activation of chemokine receptors CXCR4 by its ligand chemokine SDF-1 results in excitation of DRG sensory neurons and in an increase in intracellular calcium concentration in animal models of neuropathic pain. Therefore we, acutely isolated DRG sensory neurons from HFD-induced diabetic mice and performed calcium imaging studies as previously described. We were able to show that application of SDF-1 chemokine increases intracellular calcium concentration in HFD-induced diabetic DRG sensory neurons, demonstrating the functional significance of CXCR4 receptor expression in DRG sensory neurons in neuropathic pain in diabetes.

My experience as R25 fellow and PTSD scholar was extremely important as it allowed me to obtain these exciting preliminary results, which I have presented at international meetings and will provide the basis for a publication but also for the application for independent mentored research awards (K08 grant). This will facilitate my transition from resident to clinician-scientist.  Most importantly, the results which I found in these years of research fellowship will shed light on the molecular mechanisms of neuropathic pain and open interesting avenues for translational research.

Research Interests:

This is my 18th year at Northwestern. My first eight years here were spent in the Medical Scientist Training Program. My dissertation research with David Mogul, PhD, examined the application of nonlinear dynamical systems theory to characterization and control of epileptiform activity in the rat hippocampus. The ultimate goal of this research was to investigate whether more sophisticated stimulation paradigms might allow us to stop epileptic seizures via electrical stimulation of the seizure focus. I showed first that in vitro epileptiform bursting had both deterministic and stochastic (random) features. I also showed that application of small, precisely-timed electrical stimuli to the hippocampus could modify the bursting pattern from a chaotic one to a (nearly) periodic one. In doing this, I implemented a novel technique for adaptively tracking the system’s “fixed point” in state space, and also developed two novel methods (state-point forcing and short time expansion) to assess for determinism in time-series data.

I chose to stay at Northwestern for my neurology residency in large part because of the support and flexibility the program provided to do research during residency. Although neurology was not affiliated with the PSTP during my residency training, I benefited greatly from the flexible scheduling and advice from our program director and chairman. During my residency training, I worked with Dr. Lee Miller for a total of eight months, and I have continued to work in his lab as an Instructor and now an Assistant Professor in Neurology. We are interested in the field of neural engineering, specifically in brain-machine interface (BMI). The ultimate goal of this research is to enable locked-in or tetraplegic patients to communicate and interact with their environment. Cortical signals are recorded, decoded using various signal processing techniques, and then used to control a computer cursor, and eventually will be used to electrically stimulate muscles so that patients can use their own arms again. The large amount of research time I spent during residency enabled me to successfully apply for an NIH K08 award for this work. Ultimately I plan to transition this bench research into translational work, and I hope it will vastly improve the quality of life of motor impaired individuals. It is gratifying to finally achieve my aspirations of a combined career in clinical medicine and research. I am grateful to the neurology department at Northwestern for facilitating my career path to physician-scientist.

Research Interests:

Investigating predictors of stroke after cardiac surgery and the long-term outcomes, including quality of life.

Research Interests:

My interest is in elucidating mechanisms of epileptogenesis. Many cases of temporal lobe epilepsy are refractory to medical treatment, highlighting the need for further study in order to develop novel treatments. Both human pathology and various animal models of temporal lobe epilepsy are marked by hippocampal dentate granule cell hyperexcitability and extensive loss of dentate hilar mossy cells. I am interested in the network formed between hippocampal granule neurons and hilar mossy cells in epileptic states. I also maintain an interest in the role of psychological factors, namely stress and anxiety, in epilepsy and seizures.